The Role of Diet in the Pathogenesis and Prognosis of Head and Neck Squamous Cell Carcinoma.

Abstract

Dietary choices likely have consequences for head and neck squamous cell carcinoma (HNSCC) prognosis but have not been thoroughly evaluated. The molecular mechanisms by which diet influences HNSCC progression and prognosis also have not been thoroughly investigated. This research was conducted in the context of the University of Michigan Head and Neck Specialized Program of Research Excellence (HN-SPORE). Longitudinal epidemiologic, clinical, and molecular data were collected from newly diagnosed HN-SPORE subjects between 2002 – 2012. Data were collected at baseline and yearly. Dietary data were collected using the Harvard food frequency questionnaire (FFQ). The first aim identified major dietary patterns in a cohort of incident HNSCC cases, and examined associations of these patterns and weight status with recurrence and survival. Dietary patterns were identified using principal components analysis. Cox proportional hazard models were fit to examine associations. Two patterns emerged: a “whole foods pattern” and a “Western pattern”. In multivariable analyses, subjects with high pretreatment whole foods pattern score, or considered overweight or obese had lower recurrence and mortality. The second aim compared pretreatment consumption of twelve micronutrients by HPV status of the tumor. Multivariable logistic regression examined these associations. In multivariable analyses, significant and positive associations were observed between vitamin A, vitamin E, iron, β-carotene and folate intake and HPV-positive status. The third aim examined associations between pretreatment dietary patterns, reported and serum levels of carotenoids and vitamin E, and presence of cachexia with pretreatment serum proinflammatory cytokine levels. In multivariable analyses, higher whole foods pattern scores and reported total carotenoid intake were significantly associated with lower levels of IL-6, TNF-α, and IFN-γ. Lower IFN-γ levels were associated with increasing serum α-tocopherol levels. In summary, high pretreatment whole foods pattern score was associated with decreased HNSCC mortality. The reduction of proinflammatory cytokine levels is one potential mechanism underlying this association. The reported differences in micronutrient intake by HPV status provides support for the hypothesis that differences in lifestyle factors may contribute to the discrepancy in survival rates observed between subtypes. This research provides a basis for translational studies aimed at developing individualized dietary interventions to improve HNSCC disease outcomes.